Differentiation of hepatocyte-like cells from human pluripotent stem cells using small molecules

Faizal Z. Asumda, Konstantinos E. Hatzistergos, Derek M. Dykxhoorn, Silvia Jakubski, Jasmine Edwards, Emmanuel Thomas, Eugene R. Schiff

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

A variety of approaches have been developed for the derivation of hepatocyte-like cells from pluripotent stem cells. Currently, most of these strategies employ step-wise differentiation approaches with recombinant growth-factors or small-molecule analogs to recapitulate developmental signaling pathways. Here, we tested the efficacy of a small-molecule based differentiation protocol for the generation of hepatocyte-like cells from human pluripotent stem cells. Quantitative gene-expression, immunohistochemical, and western blot analyses for SOX17, FOXA2, CXCR4, HNF4A, AFP, indicated the stage-specific differentiation into definitive endoderm, hepatoblast and hepatocyte-like derivatives. Furthermore, hepatocyte-like cells displayed morphological and functional features characteristic of primary hepatocytes, as indicated by the production of ALB (albumin) and α-1-antitrypsin (A1AT), as well as glycogen storage capacity by periodic acid-Schiff staining. Together, these data support that the small-molecule based hepatic differentiation protocol is a simple, reproducible, and inexpensive method to efficiently drive the differentiation of human pluripotent stem cells towards a hepatocyte-like phenotype, for downstream pharmacogenomic and regenerative medicine applications.

Original languageEnglish (US)
Pages (from-to)16-24
Number of pages9
JournalDifferentiation
Volume101
DOIs
StatePublished - May 1 2018

Keywords

  • Hepatocyte
  • Hepatocyte-like cells
  • Human pluripotent stem cell differentiation
  • Small molecules

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology
  • Cancer Research

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